A novel 23-bp deletion in exon 5 of the p53 tumor suppressor gene

We report a novel p53 deletion in a 63-year-old female with breast cancer. Mutation screening of DNA samples, obtained from tumor specimens from 98 individuals with breast cancer, by a combined polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis showed that the index case had a somatic mutation identified to be a 23-bp deletion in exon 5 of the p53 gene. This deletion would be expected to yield a truncated and functionally inactive p53 protein molecule, probably resulting in cell transformation. The existence of 6-bp palindromic-like sequences encompassing the deleted fragment suggests that the slipped mispairing mechanism is not involved in producing the deletion, which probably resulted from palindromic pairing during replication.     

Immunohistochemical localization of interleukin-6 in peripheral human endocrine glands

Interleukin-6 (IL-6) is a pleiotropic cytokine with differentiation and growth-promoting effects. Extensive studies in experimental animals denote that IL-6 is produced in various endocrine organs and participates in the local control of endocrine cell function. The expression of this cytokine in human endocrine glands, however, has only been examined in a limited number of studies. We investigated the immunohistochemical expression and localization of IL-6 in a variety of peripheral human endocrine glands. In the adrenals, IL-6 immunoreactivity was detected in all three zones of the cortex. The reticularis and glomerulosa zones were more heavily stained as compared with the slight immunoreactivity of the fasciculata zone. In the adrenal medulla, chromaffin and sustentacular cells were variably positive. A substantial number of follicular thyroid cells were strongly immunoreactive for IL-6 in all normal and hyperplastic thyroids examined. Parafollicular cells were negative. Parathyroid chief cells were mildly positive; selective and more intense staining was observed in acidophilic cells. Pancreatic islet cells were variably positive. In the testis positive staining was selectively observed in both Leydig and Sertoli cells. In conclusion, IL-6 immunoreactivity is present in almost all the human endocrine glands and it expressed in a cell-specific manner. These observations provide further support for the existence of local immune-endocrine interactions.     

Inhibition of indoleamine 2,3-dioxygenase in mixed lymphocyte reaction affects glucose influx and enzymes involved in aerobic glycolysis and glutaminolysis in alloreactive T-cells

Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity. T-cell proliferation and differentiation to effector cells require increased glucose consumption, aerobic glycolysis and glutaminolysis. The effect of IDO on the above metabolic pathways was evaluated in alloreactive T-cells. Mixed lymphocyte reaction (MLR) in the presence or not of the IDO inhibitor, 1-methyl-dl-tryptophan (1-MT), was used. In MLRs, 1-MT decreased tryptophan consumption, increased cell proliferation, glucose influx and lactate production, whereas it decreased tricarboxylic acid cycle activity. In T-cells, from the two pathways that could sense tryptophan depletion, i.e. general control nonrepressed 2 (GCN2) kinase and mammalian target of rapamycin complex 1, 1-MT reduced only the activity of the GCN2 kinase. Additionally 1-MT treatment of MLRs altered the expression and/or the phosphorylation state of glucose transporter-1 and of key enzymes involved in glucose metabolism and glutaminolysis in alloreactive T-cells in a way that favors glucose influx, aerobic glycolysis and glutaminolysis. Thus in alloreactive T-cells, IDO through activation of the GCN2 kinase, decreases glucose influx and alters key enzymes involved in metabolism, decreasing aerobic glycolysis and glutaminolysis. Acting in such a way, IDO could be considered as a constraining factor for alloreactive T-cell proliferation and differentiation to effector T-cell subtypes.     

Quality of life outcome of critical care survivors eighteen months after discharge from intensive care

Aim

To assess the changes in health-related quality of life in patients discharged from the intensive care unit (ICU).

Methods

At the General University ICU, Trauma Hospital in Athens, 242 patients were enrolled prospectively over a study period of 18 months. Out of these, 116 participants (47.9%) completed all survey components at 6, 12, and 18 months. We used Quality of Life-Spanish (QOL-SP) to assess the health-related quality of life. Patients or their relatives were interviewed on ICU admission and at 6, 12, and 18 months after discharge from the ICU.

Results

Mean quality of life score of the patients increased from 2.9 ± 4.8 (out of maximum 25 points) on ICU admission to 7.0 ± 7.2 points at 6 months after discharge, and then decreased to 5.6 ± 6.9 points at 18 months (P<0.001; Friedman test). Multilinear regression analysis showed that the variables which had the strongest association with the quality of life on admission were age (P = 0.002) and male sex (P = 0.001), whereas age (P<0.001), length of ICU stay (P<0.001), and male sex (P = 0.002) had the strongest association 18 months after discharge from the ICU. Survival rate was 66.9% at discharge from ICU and 61.6% at hospital discharge. There were 33% deaths in the ICU, 5.3% in the hospital, and 6.2% after ICU discharge. There were 7.4% patients lost to follow-up.

Conclusions

After discharge from the ICU, patients’ quality of life was poor and showed an improvement at 18 months after discharge, but was still worse than on admission. Age, ICU length of stay, and male sex were the factors that had the strongest impact on the quality of life on admission and at 18 months after discharge from the ICU.The cost of intensive care and limited resources directed to patients with a poor prognosis raise questions about the utilization of such resources. Since the need for intensive care in several countries exceeds its availability (1), intensive care specialists are forced to admit those patients who will benefit most. There is an increasing pressure that the assessment of long-term survival and quality of life of survivors should be incorporated into outcome evaluation of intensive care unit (ICU) (2).Instruments for assessing quality of life in critically ill patients surviving intensive care include EuroQol-5D (EQ-5D), Nottingham Health Profile (NHP), Sickness Impact Profile (SIP), Medical Outcomes Study 36-item Short Form (SF-36), and Quality Of Life-Spanish (QOL-SP) (3). These instruments aim to evaluate the aspects of health important for all patients. Several cross-sectional studies have used generic, multidimensional quality of life instruments to compare health-related quality of life of intensive care patients with the that of the general population and found a considerable deterioration in the former group (3,4). However, such evidence may be misleading if pre-hospitalization health-related quality of life is not taken into account.Quality of life is an important endpoint in assessing long-term results of intensive care, but the ideal timing for such an assessment is still unclear. This topic has been covered in some reports dealing with pre-ICU assessment of health-related quality of life (3). QOL-SP questionnaire, developed by Fernandez et al (5), is specifically designed for critically ill patients. This is one of the few instruments that have been validated in a critical care population, but it is neither widely used nor well known in the critical care community. A few studies have used QOL-SP to assess medical (6), surgical (7), or multiple trauma patients (8), and to measure the quality of life before ICU, as well as the changes in quality of life from baseline to 6 and 24 months.Despite its limitations, we used this instrument to assess the changes in health-related quality of life in people who survived critical illness in a Greek medical-surgical ICU at 6, 12, and 18 months after ICU discharge, and to compare these data with their pre-admission status.     

Treatment outcome of obstructive sleep apnea syndrome in a patient with schizophrenia: case report

A case of a patient with comorbid schizophrenia and obstructive sleep apnea syndrome (OSAS) who was treated with nasal continuous positive airway pressure (nCPAP) is presented. This treatment led to significant improvement of schizophrenic and depressive symptoms, with only a partial, albeit not trivial, effect on his cognitive functioning. These encouraging results of treatment of OSAS in schizophrenia with nCPAP suggest the need for further and more systematic investigation of sleep and its disorders in psychotic patients.     

Immunohistochemical profile of cystosarcoma phyllodes of the breast: a study of 23 cases

Cystosarcoma phyllodes (CP) of the breast is a rare biphasic tumor composed of benign epithelium and a spindle cell stroma. Biologic behavior of CP cannot be predicted with certainty on the basis of morphologic criteria only. We studied immunohistochemical expression of basic fibroblastic growth factor (bFGF), urokinase, Ki67, p53 protein, and microvessel density in stromal and epithelial components of 14 low-grade CP (LCP) and 9 high-grade CP (HCP). bFGF was more often positive in LCP than in HCP. The stroma was positive for bFGF in 86% of LCP and 67% of HCP, and the epithelium was positive in 64% of LCP and 14% of HCP. Urokinase was positive in stromal cells of 86% of LCP and 93% of HCP. The epithelial positivity for urokinase in both groups resembled closely that of the stroma. p53 protein was more often positive in stromal cells of HCP (67%) than in LCP (50%). Ki67 was positive in the stroma of 43% of LCP and 89% of HCP and in the epithelium of 14% of LCP and 33% of HCP. There was no significant difference in microvessel density (MVD) in low- and high-grade lesions. Our study demonstrates that stromal Ki67 and p53 immunohistochemical positivity are more often associated with high-grade tumors. The positive immunostaining for bFGF, urokinase, Ki67, and p53 in stroma and epithelium of the majority of CP supports the existence of epithelial-stromal interactions and recognizes epithelium as an integral part of this tumor.     

Gastric emptying in very-low-birth-weight infants treated with nasal continuous positive airway pressure

OBJECTIVE: Nasal continuous positive airway pressure (NCPAP) is frequently used for prolonged periods in very low birth weight infants. We asked if NCPAP affects gastric emptying. STUDY DESIGN: Preterm newborn infants (n = 16) with a mean body weight of 935 g (SD, 155) and a mean gestational age of 27.7 weeks (SD, 1.9) were treated with NCPAP and fed by orogastric tube. A comparison group of 20 newborn infants with a mean body weight of 1090 grams (SD, 130) and a mean gestational age of 28.2 weeks (SD, 1.2) were not receiving NCPAP. All newborn infants received a milk formula containing 81 kcal/dL given in similar quantities. The antral cross-sectional area was measured by means of an ultrasound technique. RESULTS: Mean half-time of antral cross-sectional area was 28 minutes (SD, 12) in the NCPAP group and 40 minutes (SD, 17) in the comparison group ( P < .05). There were no differences in gastrointestinal complications between the two groups. CONCLUSIONS: The gastric emptying time was shorter for newborn infants treated with NCPAP.     

Responsiveness to peripherally administered melanocortins in lean and obese mice

To elucidate mechanisms of melanocortin action, we investigated the effects of a melanocortin receptor agonist (melanotetan II [MTII]) in lean C57BL/6J and obese (DIO, ob/ob, UCP1-DTA) mice. MTII administration (100 microg q.i.d. i.p.) for 24 h results in similar weight loss but a more pronounced decrease of food intake in DIO mice. After 4 and 8 days of MTII treatment, however, the reduction in both food intake and body weight is more pronounced in DIO mice than in lean mice. MTII administration for 24 h prevents food deprivation-induced alterations in hypothalamic neuropeptide Y (NPY) and liver adiponectin receptor 1 and adiponectin receptor 2 mRNA expression, but does not alter hypothalamic mRNA expression of melanocortin 4 receptor or adiponectin serum and mRNA expression levels. NPY and agouti gene-related protein (AgRP) mRNA expression after 8 days of MTII is increased to levels comparable to pair-fed mice. In summary, 1) MTII is an effective treatment for obesity and related metabolic defects in leptin-resistant (DIO, UCP1-DTA) and leptin-sensitive (ob/ob) mouse models of obesity; 2) the effects of MTII on food intake and body weight are more pronounced in DIO mice than in lean mice; 3) the tachyphylactic effect after prolonged MTII administration appears to be, at least in part, caused by a compensatory upregulation of NPY and AgRP mRNA levels, whereas decreasing leptin levels may play a very minor role in mediating tachyphylaxis; and 4) alterations in adiponectin receptor mRNA expression after fasting or MTII treatment may contribute to altered insulin sensitivity and needs to be studied further.     

Greek McGill Pain Questionnaire: validation and utility in cancer patients

In 1968, Melzack and Casey suggested that there are three major psychological dimensions of pain: sensory, affect, evaluative. These categories interact with one another to provide quantitative and qualitative information on the components of pain. In 1975, Melzack developed the McGill Pain Questionnaire, which is composed of four major parts and evaluates the qualities of pain. The aim of this study was to assess the applicability, reliability, and validity of the McGill Pain Questionnaire on a sample of Greek cancer patients receiving palliative treatment. It was administered to 114 cancer patients before the initiation of the palliative treatment, and then to 80 cancer patients during the treatment 7 days later. The results indicated that scale reliability was very good (0.95-0.97). During the pretreatment period, correlations between Present Rating Index (PRI), Present Pain Intensity (PPI), and Number of Words Chosen (NWC) ranged between 0.42 and 0.92. During the post-treatment time, the correlations ranged between 0.28 and 0.91. Only 21.8% of the words met a criterion of 30% for representativeness on the first administration of the questionnaire, and 9% met this criterion on the second. Validity was satisfactory (P < 0.005) according to "responsiveness to changes in time", as there was a statistical difference between the pretreatment and post-treatment time. Patients presented a desirable level of convergent construct validity (P < 0.05) concerning their performance status. Exploratory factor analysis was examined and two factors with eigenvalue over 1 were extracted, and they accounted for 95.2% of the variance. These results support the Greek-MPQ as a reliable and valid measure for evaluating the qualities of cancer pain in patients receiving palliative care.